ω-Aryl-cis-13-PGF compounds

ABSTRACT

This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is of the cis configuration. Also provided in this invention, are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

The present application is a divisional application of Ser. No. 774,186,filed Mar. 3, 1977, which is a divisional application of Ser. No.595,869, filed July 14, 1975, now issued as U.S. Pat. No. 4,026,909 onMay 31, 1977.

The present invention relates to prostaglandin analogs for which theessential material constituting disclosure therefor is incorporated byreference here from Ser. No. 595,869, filed July 14, 1975, now issued asU.S. Pat. No. 4,026,909.

I claim:
 1. A prostaglandin analog of the formula: ##STR1## WHEREIN D is##STR2## wherein R₈ is hydrogen or hydroxy; WHEREIN Y iscis-CH═CH--;wherein Z₆ is(1) cis-CH═CH--CH₂ --(CH₂)_(g) --CH₂ --, (2)cis-CH═CH--CH₂ --(CH₂)_(g) --CF₂ --, (3) cis-CH₂ --CH═CH--(CH₂)_(g)--CH₂ --, (4) --(ch₂)₃ --(ch₂)_(g) --(CH₂ --, or (5) --(CH₂)₃--(CH₂)_(g) --CF₂ --, wherein g is one, 2, or 3; Wherein Z₃ is oxa ormethylene; Wherein T is chloro, fluoro, trifluoromethyl, alkyl of one to3 carbon atoms, inclusive, or alkoxy of one to 3 carbon atoms,inclusive, and s is zero, one, 2, or 3, the various T's being the sameor different, with the proviso that not more than two T's are other thanalkyl; Wherein M₁ is ##STR3## wherein R₅ and R₆ are hydrogen or methyl,with the proviso that one of R₅ and R₆ is methyl only when the other ishydrogen; Wherein L₁ is ##STR4## wherein R₃ and R₄ are hydrogen, methyl,or fluoro, being the same or different, with the proviso that one of R₃and R₄ is fluoro only when the other is hydrogen or fluoro and Z₃ ismethylene; and Wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms,inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, two,or three chloro or alkyl of one to 3 carbon atoms, inclusive, or apharmacologically acceptable cation.
 2. A compound according to claim 1,wherein D is ##STR5##
 3. A compound according to claim 1, wherein D is##STR6##
 4. A compound according to claim 3, wherein Z₃ is methylene. 5.A compound according to claim 4, wherein s is zero or one and T ischloro, fluoro, or trifluoromethyl.
 6. A compound according to claim 3,wherein Z₃ is oxa.
 7. A compound according to claim 6, wherein s iszero.
 8. A compound according to claim 7, wherein s is zero or one and Tis chloro, fluoro, or trifluoromethyl.
 9. A compound according to claim8, wherein Z₆ is cis-CH═CH--CH₂ --(CH₂)_(g) --CF₂ --.
 10. A compoundaccording to claim 8, wherein Z₆ is cis-CH₂ --CH═CH--(CH₂)_(g) --CH₂ --.11. A compound according to claim 8, wherein Z₆ is cis-CH═CH--CH₂--(CH₂)_(g) --CH₂ --.
 12. A compound according to claim 11, wherein M₁is ##STR7##
 13. A compound according to claim 12, wherein g is one. 14.A compound according to claim 13, wherein R₃, R₄, R₅, and R₆ are allhydrogen.
 15. 15-epi-16-Phenoxy-17,18,19,20-tetranor-cis-13-PGF₂α,methyl ester, a compound according to claim
 14. 16. A compound accordingto claim 11, wherein M₁ is ##STR8##
 17. A compound according to claim16, wherein g is three.
 18. A compound according to claim 16, wherein gis one.
 19. A compound according to claim 18, wherein R₃ and R₄ are bothhydrogen.
 20. A compound according to claim 19, wherein R₅ is methyl.21. 16-Phenoxy-17,18,19,20-tetranor-15-methyl-cis-13-PGF₂α, a compoundaccording to claim
 20. 22.16-Phenoxy-17,18,19,20-tetranor-15-methyl-cis-13-PGF₂α, methyl ester, acompound according to claim
 20. 23. A compound according to claim 19,wherein R₆ is methyl.
 24. 16-Phenoxy-17,18,19,20-tetranor-cis-13-PGF₂α,15-methyl ether, a compound according to claim
 23. 25.16-Phenoxy-17,18,19,20-tetranor-cis-13-PGF₂α, methyl ester, 15-methylether, a compound according to claim
 23. 26. A compound according toclaim 19, wherein R₅ , 6 are both hydrogen. 27.16-Phenoxy-17,18,19,20-tetranor-cis-13-PGF₂α, a compound according toclaim
 26. 28. 16-Phenoxy-17,18,19,20-tetranor-cis-13-PGF₂α, methylester, a compound according to claim
 26. 29. A compound according toclaim 18, wherein at least one of R₃ and R₄ is methyl.
 30. A compoundaccording to claim 29, wherein R₃ and R₄ are both methyl.
 31. A compoundaccording to claim 30, wherein R₅ is methyl. 32.16-Phenoxy-18,19,20-trinor-15,16-dimethyl-cis-13-PGF₂α, methyl ester, acompound according to claim
 31. 33. A compound according to claim 30,wherein R₆ is methyl.
 34. 16-Phenoxy-18,19,20-trinor-16-methyl-cis-13-PGF₂α, methyl ester, 15-methyl ether, acompound according to claim
 33. 35. A compound according to claim 30,wherein R₅ and R₆ are both hydrogen. 36.16-Phenoxy-18,19,20-trinor-16-methyl-cis-13-PGF₂α, a compound accordingto claim
 35. 37. 16-Phenoxy-18,19,20-trinor-16-methyl-cis-13-PGF₂α,methyl ester, a compound according to claim 35.